FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Hympavzi™ (marstacimab-hncq) Subcutaneous injection |
For routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with:
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1 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
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Module |
Clinical Criteria for Approval |
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Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. ONE of the following: A. The requested agent is eligible for continuation of therapy AND ONE of the following:
1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR 2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR B. ALL of the following: 1. ONE of the following: A. The patient has a diagnosis of Hemophilia A (factor VIII deficiency) without factor VIII inhibitors AND BOTH of the following: 1. ONE of the following: A. The requested agent will be used for primary prophylaxis in patients with severe factor VIII deficiency (factor VIII level of less than 1%) (medical records required) OR B. The requested agent will be used for secondary prophylaxis in patients with at least TWO episodes of spontaneous bleeding into joints (medical records required) AND 2. One of the following: A. The patient has tried and had an inadequate response to BOTH of the following: 1. Hemlibra (emicizumab) AND 2. An antihemophilic Factor VIII agent OR B. The patient has tried and had an inadequate response to ONE of the following AND an intolerance or hypersensitivity to ONE of the following: 1. Hemlibra (emicizumab) AND 2. An antihemophilic Factor VIII agent OR C. The patient has an FDA labeled contraindication to BOTH Hemlibra AND ALL antihemophilic Factor VIII agents OR B. The patient has a diagnosis of Hemophilia B (factor IX deficiency) without factor IX inhibitors AND BOTH of the following: 1. ONE of the following: A. The requested agent will be used for primary prophylaxis in patients with severe factor IX deficiency (factor IX level of less than 1%) (medical records required) OR B. The requested agent will be used for secondary prophylaxis in patients with at least TWO episodes of spontaneous bleeding into joints (medical records required) AND 2. One of the following: A. The patient has tried and had an inadequate response to an antihemophilic Factor IX agent OR B. The patient has an intolerance or hypersensitivity to an antihemophilic Factor IX agent OR C. The patient has an FDA labeled contraindication to ALL antihemophilic Factor IX agents AND 2. If the patient has an FDA labeled indication, then ONE of the following: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient’s age for the requested indication AND 3. The requested agent will be used as prophylaxis to prevent or reduce the frequency of bleeding episodes AND 4. The requested agent will NOT be used for the treatment of breakthrough bleeding AND 5. The patient is NOT pregnant AND 2. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., prescriber working in a hemophilia treatment center, hematologist with hemophilia experience), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 3. The requested agent will NOT be used in combination with clotting factor products (i.e., factor VIII or factor IX concentrates) being used as prophylactic therapy (Note: Factor VIII or factor IX products can be administered for the treatment of breakthrough bleeds while receiving Hympavzi) AND 4. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 6 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND 2. ONE of the following: A. The patient has had improvement or stabilization with the requested agent as indicated by the number of breakthrough bleeding episodes (medical records required) OR B. There is support for the continued use of the requested agent (medical records required) AND 3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., prescriber working in a hemophilia treatment center, hematologist with hemophilia experience), or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND 4. The requested agent will NOT be used in combination with clotting factor products (i.e., factor VIII or factor IX concentrates) being used as prophylactic therapy (Note: Factor VIII or factor IX products can be administered for the treatment of breakthrough bleeds while receiving Hympavzi) AND 5. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
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Module |
Ops Set Up |
Validation Options |
Other Explanation |
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Documentation: Requirements as noted within the policy;Validation: Apply Baseline and go to Validation Options |
Age Verification;Continuation of Therapy;Contraind., intolerance, or hypersensitivity to prereq. |
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QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
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Module |
Clinical Criteria for Approval |
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Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: 1. The requested quantity (dose) does NOT exceed the program quantity limit OR 2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following: A. If the requested quantity (dose) is 300 mg once weekly for maintenance dosing, then BOTH of the following: 1. The patient weighs greater than or equal to 50 kg AND 2. The patient has tried and had an inadequate response (i.e., inadequate control of bleeding episodes) with the maintenance dosing of 150 mg once weekly (medical records required) OR B. If the requested quantity (dose) is NOT 300 mg once weekly for maintenance dosing, then ONE of the following: 1. BOTH of the following: A. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND B. There is support for therapy with a higher dose for the requested indication OR 2. BOTH of the following: A. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND B. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR 3. BOTH of the following: A. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND B. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months Note: If approving initial loading dose, approve quantity for loading dose plus maintenance for 1 month per FDA labeling followed by maintenance dose for the remainder of the length of approval. Maintenance dosing begins 1 week after patient receives the loading dose. |
QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
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Module |
Ops Set Up |
Validation Options |
Other Explanation |
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Documentation: Requirements as noted within the policy;Validation: Apply Baseline and go to Validation Options |
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Hemophilia A |
Hemophilia A, also called Factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective Factor VIII (FVIII), a clotting protein. Although it is passed down from mothers to children, about 1/3 of cases found have no previous family history.(2) Treatment for hemophilia A is dependent on several factors and there is not a universal therapy that will work for all patients. Clinically, the hallmark of bleeding in hemophilia is bleeding into the joints, muscles, and soft tissues. The severity and the risk of that bleeding can be correlated to the residual factor activity that can be measured in the blood. Patients with severe disease have less than 1% residual activity, and often have zero. These are the patients who are at risk for spontaneous and traumatic bleeding. Having over 5% residual amount makes bleeding into the joints very unusual (although not inconceivable), and most bleeding is triggered only by trauma. Residual activity of 1-5% appears for the most part to prevent spontaneous bleeding, but patients can still be at risk for joint bleeds with even relatively minor trauma.(3) The main goal of any therapy is to completely prevent bleeding. The current World Hemophilia Federation Guidelines for the Management of Hemophilia state:(5)
Approximately 1 in 5 people with hemophilia A will develop an antibody, called an inhibitor, to the clotting factor concentrate(s) used to treat or prevent their bleeding episodes. Developing an inhibitor is one of the most serious and costly medical complications of a bleeding disorder because it becomes more difficult to treat bleeds. Inhibitors most often appear in the first 50 exposure days of clotting factor concentrates.(3,6) The National Hemophilia Foundation classifies inhibitors as low responding and high responding in addition to low titer (less than 5 BU) and high titer (greater than or equal to 5 BU). In low responding inhibitors when the patient receives Factor VIII the inhibitor titer does not rise. These patients can be treated with higher doses of the CFC. If the inhibitor titer increases with CFC it is considered high responding. For high responding inhibitors, the situation becomes much more complicated as even large doses of infused CFC are often rendered ineffectual by the sheer potency of the antibody response.(4) |
Hemophilia B |
Hemophilia B, or Christmas disease, is an inherited, recessive disorder that involves deficiency of functional coagulation factor IX (FIX) in plasma. Hemophilia B is caused by a variety of defects in the F9 gene. As this gene is carried on the X chromosome, the disease usually manifests in males and is transmitted by females who carry the causative mutation on one of their X chromosomes. Spontaneous mutation and acquired immunologic processes can result in this disorder, as well. Hemophilia B constitutes about 20% of hemophilia cases. Hemophilia B may be classified as severe, moderate, or mild, based on the plasma levels of FIX (< 1%, 1-5%, 6-40%, respectively). About 50% of persons with hemophilia B have FIX levels greater than 1%.(6) Approximately 3-5% of patients with severe hemophilia B develop alloantibody inhibitors that can neutralize FIX. These inhibitors are usually immunoglobulin G antibodies and appear after the first infusions of FIX concentrate. Both genetic and environmental factors determine the frequency of inhibitor development. Inhibitors most often appear during the first 50 times a person is treated with clotting factor concentrates, but they can appear at any time.(6,7) Factor IX is the treatment of choice for acute hemorrhage or presumed acute hemorrhage. Recombinant factor IX is the preferred source for replacement therapy. And while plasma-derived FIX products are still available, approximately 75% of the hemophilia community takes a recombinant FIX product. The Medical and Scientific Advisory Council (MASAC) of the National Bleeding Disorders Foundation encourages the use of recombinant clotting factor products because they are safer. Patients with severe hemophilia may be on a routine treatment regimen, called prophylaxis, to maintain enough clotting factor in their bloodstream to prevent bleeds. MASAC recommends prophylaxis as optimal therapy for children with severe hemophilia B. Aminocaproic acid is an antifibrinolytic, preventing the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds. Other therapies include gene therapy, desmopressin, and newer prophylaxis medications.(6,7) |
Efficacy |
Hympavzi (marstacimab-hncq) is a human monoclonal IgG1 antibody directed against the Kunitz domain 2 (K2) of TFPI to neutralize TFPI activity and enhance coagulation. TFPI is the primary inhibitor of the extrinsic coagulation cascade and negatively regulates thrombin generation within the extrinsic pathway of coagulation by inactivating the protease functions of FXa/FVIIa/TF complex. TFPI binds to and inhibits the factor Xa active site via its second Kunitz inhibitor domain (K2).(1) The efficacy of Hympavzi was established in 116 adult and pediatric patients (aged 12 years and older and less than or equal to 35 kg) with severe hemophilia A without FVIII inhibitors or severe hemophilia B without FIX inhibitors enrolled in the BASIS study (NCT03938792), an open-label, multi-center, two-phase study. Severe hemophilia is defined as factor activity less than 1%. Patients with a history of coronary artery disease, venous or arterial thrombosis or ischemic disease were excluded from the study. Following screening, patients entered a 6-month observation phase and were enrolled to two cohorts based on the factor replacement treatment they were receiving prior to study entry: on-demand or routine prophylaxis. Patients who completed the observation phase were to receive 12 months of Hympavzi. Of the 116 patients who received Hympavzi, 33 patients were in the on-demand treatment cohort and 83 were in the prophylactic treatment with FVIII or FIX cohort during the observation phase.(1) Patients received an initial 300 mg loading dose of Hympavzi followed by maintenance doses of 150 mg of Hympavzi once weekly for 12 months. Dose escalation to 300 mg of Hympavzi once weekly was permitted after 6 months of treatment in patients weighing greater than or equal to 50 kg and experiencing greater than or equal to 2 breakthrough bleeds. Fourteen (12%) underwent dose escalation. The mean annualized bleeding rates (ABRs) for treated bleeds were 38 and 7.85 in the observational phase for the on-demand and prophylaxis cohorts, respectively. All patients in the on-demand cohort had one or more target joints at study entry and 36% had 3 or more target joints at study entry. In the routine prophylaxis cohort, 57% of the patients had one or more target joints at study entry and 16% had 3 or more target joints at study entry.(1) Among the 116 patients treated with Hympavzi in the BASIS study, the mean age was 32 years (range 13 to 66); 19 patients were 12 to <18 years of age and all were male. The patient population included 91 with hemophilia A and 25 with hemophilia B. The efficacy of Hympavzi for each cohort was based upon the ABR of treated bleeds during treatment with Hympavzi compared to ABR during the observational phase. Other objectives of the study included evaluation of Hympavzi prophylaxis on the incidences of spontaneous bleeds, joint bleeds, target joint bleeds and total bleeds. Hympavzi prophylaxis demonstrated superiority over on-demand factor-based therapy in incidences of treated bleeds, spontaneous bleeds, joint bleeds, total bleeds and target joint bleeds.(1) Hympavzi prophylaxis demonstrated non-inferiority to routine prophylactic factor-based therapy as measured by ABR of treated bleeds as well as incidences of spontaneous bleeds, joint bleeds, target joint bleeds and total bleeds.(1) |
Safety |
Hympavzi has no FDA labeled contraindications for use.(1) |
Number |
Reference |
1 |
Hympavzi prescribing information. Pfizer. October 2024. |
2 |
Hemophilia A | NBDF. National Bleeding Disorders Foundation. https://www.bleeding.org/bleeding-disorders-a-z/types/hemophilia-a |
3 |
One size does not fit all: Individualized therapy | NBDF. National Bleeding Disorders Foundation. Published February 8, 2017. https://www.hemophilia.org/educational-programs/education/online-education/one-size-does-not-fit-all-individualized-therapy |
4 |
Kovalich D, Goto S, National Hemophilia Foundation, et al. Living With an Inhibitor: Your Guide to Managing Hemophilia With Inhibitors.; 2023. https://www.bleeding.org/sites/default/files/document/files/living-with-inhibitors.pdf |
5 |
Srivastave A, Santagostino E, Dougall A, et al. World Federation of Hemophilia Guidelines for the Management of Hemophilia. 3rd edition. August 2020. |
6 |
Hemophilia B | NBDF. National Bleeding Disorders Foundation. https://www.bleeding.org/bleeding-disorders-a-z/types/hemophilia-b |
7 |
Testing for inhibitors and hemophilia. Hemophilia. Published May 15, 2024. https://www.cdc.gov/hemophilia/testing/testing-for-inhibitors-and-hemophilia.html?CDC_AAref_Val=https://www.cdc.gov/ncbddd/hemophilia/inhibitors.html |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
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8510505020D5 |
Hympavzi |
marstacimab-hncq subcutaneous soln auto-inj |
150 MG/ML |
M ; N ; O ; Y |
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POLICY AGENT SUMMARY QUANTITY LIMIT
Wildcard |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
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8510505020D520 |
Hympavzi |
marstacimab-hncq subcutaneous soln auto-inj |
150 MG/ML |
4 |
Pens |
28 |
DAYS |
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